The overall goal of this project is to identify potent, selective, and bioactive small molecule inhibitors of both wild type and mutant variants of NSD2 for use as chemical probes and starting points for therapeutic development. During this period, the project team evaluated the activities of hit compounds previously identified by quantitative high-throughput screening. The compounds were interrogated by a variety of biochemical and cell-based assays. Additional NSD2 activity assays have been evaluated for potential use in a large-scale high-throughput screen. Biophysical studies have begun for detailed mechanistic studies of interactions between active compounds and the NSD2 SET domain.